The mission of the Comprehensive Cancer Center at St. Jude Children's Research Hospital (SJCCC) is to advance cures and means of prevention for pediatric cancer: the leading cause of disease-related death in children aged 1 to 14 years. For 36 of our 50 year history, we have pursued this mission with the support of a Cancer Center Support Grant from the National Cancer Institute (NCI). We remain the only NCI designated Cancer Center that is dedicated solely to the research and treatment of pediatric malignancies. As such, we serve as a national and international resource for health care providers, children with cancer, and their families. Through the support of the American Lebanese and Syrian Associated Charities (ALSAC), a separate corporation whose sole purpose is to raise money in support of St. Jude Children's Research Hospital (SJCRH), patients are accepted without regard to race, religion or ability to pay. Seventy-five percent of the total institutional space and annual budget are invested in the SJCCC. The current application proposes five multidisciplinary research Programs that are organized with the specific intent of translating basic science discoveries into curative therapies for children with cancer, while minimizing long-term side effects: our three disease-oriented Programs focus on Developmental Biology and Solid Tumors (DBSTP), Hematological Malignancies (HMP), and Neurobiology and Brain Tumors (NBTP); our Cancer Prevention and Control Program (CPCP) strives to improve the quality of life of individuals surviving childhood cancer; and our new Cancer Genetics, Biochemistry and Cell Biology Program (CGBCBP), formed by merging our two prior basic laboratory research Programs, embeds basic cancer research within the heart of the SJCCC, facilitating direct interaction between the disease-oriented Programs and the major laboratory resources in the Center. Research by the 144 aligned members is supported by 10 Shared Resources and an outstanding clinical research infrastructure. During the previous funding period, a new Director was appointed and several enhancements were made to the overall structure, policies, and procedures of the SJCCC. 32,522 clinical trial enrollments occurred at the Center during the current funding period, of which 56% were to SJCCC investigator initiated studies. External peer reviewed trials, many which are SJCCC member-led, accounted for another 38% of enrollments. SJCCC members published more than 2,100 manuscripts during the funding period, and in the last 12 months were supported by $69.4 million in extramural funding ($57 million, peer-reviewed; $12.4 million, non-peer-reviewed).